Glycosylated proteins are integral components of animal cell plasma membranes. While the biological importance of membrane glycoproteins is strongly implicated, not all of the reactions involved in the synthesis and transfer of the glycose portion to asparagine residues on these proteins have been determined. Unlike the serine-linked sugars and the external sugars (galactose, fucose, sialic acid, and N-acetylglucosamine) of the asparagine-linked glycose chains, all of which are transferred to the protein in a stepwise fashion, the core region of asparagine-linked glycoproteins containing mannose and N-acetylglucosamine is preassembled on a cellular phosphoisoprenoid lipid (dolichol-phosphate) into an oligosaccharide and then transferred en bloc to the asparagine moiety of the protein. Our approach to the study of these reactions has been to biochemically characterize mutant mammalian cell lines which are defective in the glycosylation of the core region of the asparagine-linked membrane glycoproteins. We have been studying the biosynthesis of membrane proteins in Chinese hamster ovary cell mutants which were selected for resistance to the cytotoxicity of the lectin concanavalin A, which has a simple sugar specificity toward alpha-glucosyl and alpha-mannosyl residues. We are attempting to determine the primary biochemical defect in these lectin-resistant cells.